The CREB binding protein (CBP) and its homolog p300 have been identified as coactivators for a number of transcription factors including CREB, AP-1 and the nuclear hormone receptors. CBP/p300 have been shown to directly interact with the general transcription machinery suggesting that CBP/p300 may function as a "bridging factor" between transcription factors and the general transcription machinery. Microinjection of CBP/p300 specific antibodies prevents CBP from functioning as a coactivator and consequently inhibits CREB, AP-1 and nuclear receptor signaling, suggesting that CBP is a necessary cofactor for these signaling pathways. It has been suggested that the negative cross-talk which is observed between these different signaling pathways may result from competition for limiting amounts of CBP. The results of this study will help determine the extent to which these signaling pathways impinge on each others activities and may suggest that we need to examine these pathways as a larger network instead of individually.